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TRPV4

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https://www.readbyqxmd.com/read/28225032/4-isopropylcyclohexanol-has-potential-analgesic-effects-through-the-inhibition-of-anoctamin-1-trpv1-and-trpa1-channel-activities
#1
Yasunori Takayama, Hidemasa Furue, Makoto Tominaga
Interactions between calcium-activated chloride channel anoctamin 1 (ANO1) and transient receptor potential vanilloid 1 (TRPV1) enhance pain sensations in mice, suggesting that ANO1 inhibition could have analgesic effects. Here we show that menthol and the menthol analogue isopropylcyclohexane (iPr-CyH) inhibited ANO1 channels in mice. The iPr-CyH derivative 4-isopropylcyclohexanol (4-iPr-CyH-OH) inhibited mouse ANO1 currents more potently than iPr-CyH. Moreover, 4-iPr-CyH-OH inhibited the activities of TRPV1, TRP ankyrin 1 (TRPA1), TRP melastatin 8 (TRPM8) and TRPV4...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205608/blockage-of-transient-receptor-potential-vanilloid-4-alleviates-myocardial-ischemia-reperfusion-injury-in-mice
#2
Qian Dong, Jing Li, Qiong-Feng Wu, Ning Zhao, Cheng Qian, Dan Ding, Bin-Bin Wang, Lei Chen, Ke-Fang Guo, Dehao Fu, Bing Han, Yu-Hua Liao, Yi-Mei Du
Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+)-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 can alleviate myocardial I/R injury in mice. TRPV4 expression began to increase at 1 h, reached statistically at 4 h, and peaked at 24-72 h. Treatment with the selective TRPV4 antagonist HC-067047 or TRPV4 knockout markedly ameliorated myocardial I/R injury as demonstrated by reduced infarct size, decreased troponin T levels and improved cardiac function at 24 h after reperfusion...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202366/modulation-of-the-trpv4-ion-channel-as-a-therapeutic-target-for-disease
#3
REVIEW
Megan S Grace, Sara J Bonvini, Maria G Belvisi, Peter McIntyre
Transient Receptor Potential Vanilloid 4 (TRPV4) is a broadly expressed, polymodally gated ion channel that plays an important role in many physiological and pathophysiological processes. TRPV4 knockout mice and several synthetic pharmacological compounds that selectively target TRPV4 are now available, which has allowed detailed investigation in to the therapeutic potential of this ion channel. Results from animal studies suggest that TRPV4 antagonism has therapeutic potential in oedema, pain, gastrointestinal disorders, and lung diseases such as cough, bronchoconstriction, pulmonary hypertension, and acute lung injury...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28187982/the-renal-trpv4-channel-is-essential-for-adaptation-to-increased-dietary-potassium
#4
Mykola V Mamenko, Nabila Boukelmoune, Viktor N Tomilin, Oleg L Zaika, V Behrana Jensen, Roger G O'Neil, Oleh M Pochynyuk
To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28158279/analysis-of-trpv-channel-activation-by-stimulation-of-fc%C3%AE%C2%B5ri-and-mrgpr-receptors-in-mouse-peritoneal-mast-cells
#5
A Solís-López, U Kriebs, A Marx, S Mannebach, W B Liedtke, M J Caterina, M Freichel, V V Tsvilovskyy
The activation of mast cells (MC) is part of the innate and adaptive immune responses and depends on Ca2+ entry across the plasma membrane, leading to the release of preformed inflammatory mediators by degranulation or by de novo synthesis. The calcium conducting channels of the TRPV family, known by their thermo and osmotic sensitivity, have been proposed to be involved in the MC activation in murine, rat, and human mast cell models. So far, immortalized mast cell lines and nonspecific TRPV blockers have been employed to characterize the role of TRPV channels in MC...
2017: PloS One
https://www.readbyqxmd.com/read/28143892/activation-of-trpv4-by-dietary-apigenin-antagonizes-renal-fibrosis-in-deoxycorticosterone-acetate-doca-salt-induced-hypertension
#6
Xing Wei, Peng Gao, Yunfei Pu, Qiang Li, Tao Yang, Hexuan Zhang, Shiqiang Xiong, Yuanting Cui, Li Li, Xin Ma, Daoyan Liu, Zhiming Zhu
Hypertension-induced renal fibrosis contributes to the progression of chronic kidney disease, and apigenin, an anti-hypertensive flavone that is abundant in celery, acts as an agonist of transient receptor potential vanilloid 4 (TRPV4). However, whether apigenin reduces hypertension-induced renal fibrosis, as well as the underlying mechanism, remain elusive. In this study, the deoxycorticosterone acetate (DOCA)-salt hypertension model was established in male Sprague-Dawley rats that were treated with apigenin or vehicle for 4 weeks...
January 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28143710/hepatic-and-renal-mechanisms-underlying-the-osmopressor-response
#7
Tu H Mai, Emily M Garland, André Diedrich, David Robertson
Increased blood pressure (BP) is observed in patients with impaired baroreflexes after water drinking. The stimulus for this effect is low blood osmolality, and it has been termed the osmopressor response (OPR). The BP increase is associated with activation of the sympathetic nervous system and a requirement for transient receptor potential vanilloid 4 (TRPV4) channels. However, the mechanisms underlying the OPR are poorly understood. We tested the hypothesis that hypotonicity is sensed in the portal area to initiate the OPR...
January 27, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28135189/direct-measurement-of-trpv4-and-piezo1-activity-reveals-multiple-mechanotransduction-pathways-in-chondrocytes
#8
M Rocio Servin-Vences, Mirko Moroni, Gary R Lewin, Kate Poole
The joints of mammals are lined with cartilage, comprised of individual chondrocytes embedded in a specialized extracellular matrix. Chondrocytes experience a complex mechanical environment and respond to changing mechanical loads in order to maintain cartilage homeostasis. It has been proposed that mechanically gated ion channels are of functional importance in chondrocyte mechanotransduction; however, direct evidence of mechanical current activation in these cells has been lacking. We have used high-speed pressure clamp and elastomeric pillar arrays to apply distinct mechanical stimuli to primary murine chondrocytes, stretch of the membrane and deflection of cell-substrate contacts points, respectively...
January 30, 2017: ELife
https://www.readbyqxmd.com/read/28122715/primary-cilia-regulate-the-osmotic-stress-response-of-renal-epithelial-cells-through-trpm3
#9
Brian J Siroky, Nancy K Kleene, Steven J Kleene, Charles D Varnell, Raven G Comer, Jialiu Liu, Lu Lu, Nolan W Pachciarz, John J Bissler, Bradley P Dixon
Primary cilia sense environmental conditions including osmolality, but whether cilia participate in osmotic response in renal epithelial cells is not known. Transient receptor potential (TRP) channels TRPV4 and TRPM3 are osmoresponsive. TRPV4 localizes to cilia in certain cell types, while renal subcellular localization of TRPM3 is not known. We hypothesized that primary cilia are required for maximal activation of the osmotic response of renal epithelial cells, and that ciliary TRPM3 and TRPV4 mediate that response...
January 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28103434/analgesic-effect-of-quetiapine-in-a-mouse-model-of-cancer-induced-bone-pain
#10
Mi Hwa Heo, Jin Young Kim, Ilseon Hwang, Eunyoung Ha, Keon Uk Park
Background/Aims: Cancer-induced bone pain (CIBP) is one of the most common pains in patients with advanced neoplasms. Because of treatment-associated side effects, more than half of cancer patients are reported to have inadequate and undermanaged pain control. New mechanism-based therapies must be developed to reduce cancer pain. Quetiapine is a commonly used atypical antipsychotic drug. We report a study of the potential analgesic effects of quetiapine in a mouse model of CIBP and examine the mechanism of bone pain by analyzing the expression of various nociceptors...
January 20, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28098409/trpv4-contributes-to-resting-membrane-potential-in-retinal-m%C3%A3-ller-cells-implications-in-cell-volume-regulation
#11
Vanina Netti, Juan Fernández, Maia Kalstein, Alejandro Pizzoni, Gisela Di Giusto, Valeria Rivarola, Paula Ford, Claudia Capurro
Neural activity alters osmotic gradients favoring cell swelling in retinal Müller cells. This swelling is followed by a regulatory volume decrease (RVD), partially mediated by an efflux of KCl and water. The transient receptor potential channel 4 (TRPV4), a nonselective calcium channel, has been proposed as a candidate for mediating intracellular Ca(2+) elevation induced by swelling. We previously demonstrated in a human Müller cell line (MIO-M1) that RVD strongly depends on ion channel activation and, consequently, on membrane potential (Vm )...
January 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28077439/the-functional-expression-of-transient-receptor-potential-channels-in-the-mouse-endometrium
#12
Katrien De Clercq, Charlotte Van den Eynde, Aurélie Hennes, Rieta Van Bree, Thomas Voets, Joris Vriens
STUDY QUESTION: Does mouse endometrial epithelial cells and stromal cells have a similar transient receptor potential (TRP)-channel expression profile and to that found in the human endometrium? SUMMARY ANSWER: Mouse endometrial epithelial and stromal cells have a distinct TRP channel expression profile analogous to what has been found in human endometrium, and hence suggests the mouse a good model to investigate the role of TRP channels in reproduction. WHAT IS KNOWN ALREADY: An optimal intercellular communication between epithelial and stromal endometrial cells is crucial for successful reproduction...
January 6, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28076819/full-spectral-multiplexing-of-bioluminescence-resonance-energy-transfer-in-three-trpv-channels
#13
Hermanus Johannes Ruigrok, Guillaume Shahid, Bertrand Goudeau, Florence Poulletier de Gannes, Emmanuelle Poque-Haro, Annabelle Hurtier, Isabelle Lagroye, Pierre Vacher, Stéphane Arbault, Neso Sojic, Bernard Veyret, Yann Percherancier
Multiplexed bioluminescence resonance energy transfer (BRET) assays were developed to monitor the activation of several functional transient receptor potential (TRP) channels in live cells and in real time. We probed both TRPV1 intramolecular rearrangements and its interaction with Calmodulin (CaM) under activation by chemical agonists and temperature. Our BRET study also confirmed that: (1) capsaicin and heat promoted distinct transitions, independently coupled to channel gating, and that (2) TRPV1 and Ca(2+)-bound CaM but not Ca(2+)-free CaM were preassociated in resting live cells, while capsaicin activation induced both the formation of more TRPV1/CaM complexes and conformational changes...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28073835/mechanosensitive-transient-receptor-potential-vanilloid-4-regulates-dermatophagoides-farinae-induced-airway-remodeling-via-2-distinct-pathways-modulating-matrix-synthesis-and-degradation
#14
Farai Gombedza, Vinay Kondeti, Nosayba Al-Azzam, Stephanie Koppes, Ernest Duah, Prachi Patil, Madison Hexter, Daniel Phillips, Charles K Thodeti, Sailaja Paruchuri
Contributions of mechanical signals to airway remodeling during asthma are poorly understood. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, has been implicated in cardiac and pulmonary fibrosis; however, its role in asthma remains elusive. Employing a Dermatophagoides farinae-induced asthma model, we report here that TRPV4 knockout mice were protected from D. farinae-induced airway remodeling. Furthermore, lung fibroblasts that were isolated from TRPV4 knockout mice showed diminished differentiation potential compared with wild-type mice...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28060940/clock-genes-regulate-the-circadian-expression-of-piezo1-trpv4-connexin26-and-vnut-in-an-ex-vivo-mouse-bladder-mucosa
#15
Tatsuya Ihara, Takahiko Mitsui, Yuki Nakamura, Satoru Kira, Hiroshi Nakagomi, Norifumi Sawada, Yuri Hirayama, Keisuke Shibata, Eiji Shigetomi, Yoichi Shinozaki, Mitsuharu Yoshiyama, Karl-Erik Andersson, Atsuhito Nakao, Masayuki Takeda, Schuichi Koizumi
OBJECTIVES: ClockΔ19/Δ19 mice is an experimental model mouse for nocturia (NOC). Using the bladder mucosa obtained from ClockΔ19/Δ19 mice, we investigated the gene expression rhythms of mechanosensory cation channels such as transient receptor potential cation channel subfamily V member 4 (TRPV4) and Piezo1, and main ATP release pathways including vesicular nucleotide transporter (VNUT) and Connexin26(Cx26), in addition to clock genes. MATERIALS AND METHODS: Eight- to twelve-week-old male C57BL/6 mice (WT) and age- and sex-matched C57BL/6 ClockΔ19/Δ19 mice, which were bred under 12-h light/dark conditions for 2 weeks, were used...
2017: PloS One
https://www.readbyqxmd.com/read/28030558/loss-of-trpv4-function-suppresses-inflammatory-fibrosis-induced-by-alkali-burning-mouse-corneas
#16
Yuka Okada, Kumi Shirai, Masayasu Miyajima, Peter S Reinach, Osamu Yamanaka, Takayoshi Sumioka, Masahide Kokado, Katsuo Tomoyose, Shizuya Saika
In humans suffering from pulmonary disease and a mouse model, transient receptor potential vanilloid 4 (TRPV4) channel activation contributes to fibrosis. As a corneal alkali burn induces the same response, we determined if such an effect is also attributable to TRPV4 activation in mice. Accordingly, we determined if the alkali burn wound healing responses in wild-type (WT) mice are different than those in their TRPV4-null (KO) counterpart. Stromal opacification due to fibrosis in KO (n = 128) mice was markedly reduced after 20 days relative to that in WT (n = 157) mice...
2016: PloS One
https://www.readbyqxmd.com/read/28028935/renoprotection-focus-on-trpv1-trpv4-trpc6-and-trpm2
#17
REVIEW
L Markó, M Mannaa, T N Haschler, S Krämer, M Gollasch
Members of the transient receptor potential (TRP) cation channel receptor family have unique sites of regulatory function in the kidney which enables them to promote regional vasodilatation and controlled Ca(2+) influx into podocytes and tubular cells. Activated TRP vanilloid 1 receptor channels (TRPV1) have been found to elicit renoprotection in rodent models of acute kidney injury following ischaemia/reperfusion. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6) in podocytes is involved in chronic proteinuric kidney disease, particularly in focal segmental glomerulosclerosis (FSGS)...
March 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28007573/5-6-%C3%AE-dhtl-a-stable-metabolite-of-arachidonic-acid-is-a-potential-edhf-that-mediates-microvascular-dilation
#18
Reut Levi-Rosenzvig, Andreas M Beyer, Joseph Hockenberry, Rotem Shelly Ben-Shushan, Dimitry Chuyun, Shahar Atiya, Snait Tamir, David D Gutterman, Andrea Szuchman-Sapir
OBJECTIVE: Prominent among the endothelium-derived hyperpolarizing factors (EDHFs) are the Cytochrome P450 (CYP) epoxygenase-derived arachidonic acid metabolites-the epoxyeicosatrienoic acids (EETs), that are known as vasodilators in the microcirculation. Among the EET isomers, 5,6-EET undergoes rapid lactonization in aqueous solution to the more stable 5,6-δ DHTL (5,6-dihydroxytrienoic lactone) isomer. It is unclear whether this metabolic transformation maintains its vasodilator potential and what is the mechanism of action...
December 19, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27989888/trpv4-antagonist-gsk2193874-does-not-modulate-cough-response-to-osmotic-stimuli
#19
Tomas Buday, Lea Kovacikova, Robert Ruzinak, Jana Plevkova
Osmolarity changes of airway superficial fluid are associated with cough and are used in research. TRPV4 is calcium channel initially described as osmosensor. In the airways, it can play role in increasing cough reflex sensitivity. The aim of our study was to test whether cough to osmotic stimuli is mediated via TRPV4 channel. Cough response was measured in 12 male guinea pigs by inhalation of saline, distilled water, hypertonic solution and citric acid for 10min in whole-body plethysmograph. Data were obtained in naïve animals and after pre-treatment with selective TRPV4 antagonist GSK2193874 in doses 300μg/kg (GSK300) and 900μg/kg (GSK900)...
February 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/27978803/magnesium-in-pain-research-state-of-the-art
#20
Dragana Srebro, Sonja Vučković, Aleksandar Milovanović, Jovan Košutić, Katarina Savić Vujović, Milica Prostran
Magnesium has been shown to produce an antinociceptive effect on animal models of neuropathic and inflammatory pain. It has also been shown to exert an analgesic effect on humans in conditions presenting acute (postoperative pain) and chronic (neuropathic) pain. As it is known that magnesium is a physiological antagonist of the N-methyl-D-aspartate (NMDA) receptor ion channel, and that the NMDA receptor plays a key role in central sensitization, the primary mechanism through which magnesium produces its analgesic effect is believed to be blockade of the NMDA receptor in the spinal cord...
December 12, 2016: Current Medicinal Chemistry
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